Pool-packaged AAV libraries exhibit extensive length-dependent and homology-dependent chimerism
Adeno-associated viruses (AAVs) are preferred gene therapy vectors because of their versatility, durability and safety profile. Here, we demonstrate extensive chimerism, manifesting as pervasive barcode swapping, among complex recombinant AAV (rAAV) libraries that are packaged as a pool. The observed chimerism is length and homology dependent but capsid independent, in some cases affecting the majority of packaged rAAV genomes. These results have implications for the design and deployment of functional rAAV libraries.
Authors
- Jonathan T. Ting (ORCID: https://orcid.org/0000-0001-8266-0392)
- Boaz P. Levi (ORCID: https://orcid.org/0000-0002-8346-872X)
- Avery C. Hunker (ORCID: https://orcid.org/0000-0003-0508-3637)
- John K. Mich (ORCID: https://orcid.org/0000-0002-1626-1139)
- Haedong Kim (ORCID: https://orcid.org/0000-0003-3589-0042)
- Chau Huynh
- Jay Shendure (ORCID: https://orcid.org/0000-0002-1516-1865)
- Troy A. McDiarmid (ORCID: https://orcid.org/0000-0002-4893-9733)
- Jean-Benoît Lalanne (ORCID: https://orcid.org/0000-0001-8753-0669)
Institutions
- Allen Institute for Brain Science (US)
- Howard Hughes Medical Institute (US)
- University of Washington (US)
- Lineage Cell Therapeutics (United States) (US)
- Brotman Baty Institute (US)
- Allen Institute (US)
- Seattle University (US)
- Université de Montréal (CA)
Publication Details
- Journal
- Nature Biotechnology
- Published
- 2026-04-28
- DOI
- https://doi.org/10.1038/s41587-026-03097-1
- Primary Topic
- Virus-based gene therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Paul G. Allen Family Foundation
- Damon Runyon Cancer Research Foundation
- Washington Research Foundation
- Cancer Research Society
- National Institutes of Health
- Natural Sciences and Engineering Research Council of Canada